Construction of multifunctional/multimodality nanoparticles for cancer diagnosis and therapy has become an attractive area of investigation. In this report, we designed a multimodality nanoprobe for cell labeling, and can be detectable by both magnetic resonance and near infrared (NIR) fluorescence imaging. Multiple hydrophobic superparamagnetic iron oxide (SPIO) nanocrystals are self-assembled into nanocomposites in water phase with the help of partially alkylated hyperbranched polycation, polyethylenimine (PEI), which already conjugated with the indocyanine dye Cy5.5 and can be used for cell imaging under NIR fluorescence imaging. The amphiphilic PEI/SPIO nanocomposites have a strong T 2 relaxivity. The iron uptake process in MCF-7/Adr displays a time dependent behavior. Confocal laser scanning microscopy reveals that the nanoprobes are internalized into the cytoplasm of MCF-7/Adr after 24 h labeling. Both MR and NIR fluorescence imaging showed strong image contrast against unlabeled cells. Under a clinical MRI scanner, labeled cells in gelatin phantom present much darker images than controlled ones. The T2 relaxation rate of the labeled cells is 98.2 s 1 , significantly higher than that of the control ones of 2.3 s 1 . This study provides an important alternative to label MCF-7/Adr at optimized low dosages with high efficiency, and may be useful to label other biologically important cells and track their behaviors in vivo.
Multifunctional nanoparticles combining diagnostic and therapeutic agents into a single platform make cancer theranostics possible and have attracted wide interests in the field. In this study, a multifunctional nanocomposite based on dextran and superparamagnetic iron oxide nanoparticles （SPIO） was prepared for drug delivery and magnetic resonance imaging （MRI）. Amphiphilic dextran was synthesized by grafting stearyl acid onto the carbohydrate backbone, and micelle was formed by the resulted amphiphilic dextran with low critical micelle concentration at 1.8 mg L^-1. Doxorubicin （DOX） and a cluster of the manganese-doped iron oxide nanoparticles （Mn-SPIO） nanocrystals were then coencapsulated successfully inside the core of dextran micelles, resulting in nanocomposites with diameter at about 100 nm. Cell culture experiments demonstrated the potential of these Mn-SPIO/DOX nanocomposites as an effective multifunctional nanoplat- lk）rm for the delivery of anticancer drug DOX with a loading content （DLC） of 16 %. Confocal laser scanning microscopy reveals that the Mn-SPIO/DOX had excellent internalization ability against MCF-7/Adr cells after 2-h labeling compared with flee DOX.HCI. Under a 3.0-T MRI scanner, Mn-SPIO/ DOX nanocomposite-labeled cells in gelatin phantom show much darker images than the control. Their transverse relaxation （T2） rate is also significantly higher than that of the control cells （33.9 versus 2.3 s^-1）. Our result offers an effective strategy to treat MCF-7/Adr at optimized low dosages with imaging capability.
Dendritic cell(DC)-based vaccines have shown promising therapeutic results in cancer and some immune disorders.It is critical to track in vivo migration behaviours of DCs and monitor the whole process dynamically and non-invasively.Superparamagnetic iron oxide(SPIO)nanoparticles are chosen for DC labelling under magnetic resonance imaging(MRI)because of their proven biosafety as contrast agents.However,when used for cell labelling,sensitive biological indicators such as cell autophagy may be helpful to better understand the process and improve the probe design.Here,lactosylated N-Alkyl polyethylenimine coated SPIO nanoparticles are used for DC labelling.This probe shows satisfactory cell labelling efficiency and low cytotoxicity.In this study,autophagy was used as a key factor to understand how DCs react to nanoparticles after labelling.Our results demonstrate that the nanoparticles can induce protective autophagy in DCs,as inhibition of the autophagy flux could lead to cell death.Meanwhile,the nanoparticles induced autophagy could promote DC maturation which is an essential process for its migration and antigen presentation.Autophagy induced DC maturation is known to enhance the vaccine functions of DCs,therefore,our results suggest that beyond the MRI tracking ability,this probe might enhance therapeutic immune activation as well.
Taipeng ShenWencheng ZhuLi YangLi LiuRongrong JinJimei DuanJames M.AndersonHua Ai
Polymer-mediated self-assembly of superparamagnetic iron oxide（SPIO） nanoparticles allows modulation of the structure of SPIO nanocrystal cluster and their magnetic properties. In this study, dopamine-functionalized polyesters（DApolyester） were used to directly control the magnetic nanoparticle spacing and its effect on magnetic resonance relaxation properties of these clusters was investigated. Monodisperse SPIO nanocrystals with different surface coating materials（poly（ε-caprolactone）, poly（lactic acid）） of different molecular weights containing dopamine（DA） structure（DA-PCL2k,DA-PCL1k, DA-PLA1k）） were prepared via ligand exchange reaction, and these nanocrystals were encapsulated inside amphiphilic polymer micelles to modulate the SPIO nanocrystal interparticle spacing. Small-angle x-ray scattering（SAXS）was applied to quantify the interparticle spacing of SPIO clusters. The results demonstrated that the tailored magnetic nanoparticle clusters featured controllable interparticle spacing providing directly by the different surface coating of SPIO nanocrystals. Systematic modulation of SPIO nanocrystal interparticle spacing can regulate the saturation magnetization（Ms） and T2 relaxation of the aggregation, and lead to increased magnetic resonance（MR） relaxation properties with decreased interparticle spacing.
Lysosomes function as important organelles within cells and their movement associates with diverse biological events, hence the real-time tracking of lysosomal movement is of great significance. However, since most ly so some fluorescent probes suffer from relatively unsatisfactory photo stability,tracking lysosomal movement in real-time remains challenging. Here,we report that a naphthalimide-based fluorescent compound,namely NIMS,is a quite promising probe for ly so some imaging. The visualizing mechanism lies in the selective accumulation of NIMS in lysosomes via a protonation reaction, followed by the fluorescence enhancement due to the interactions of NIMS with proteins. Owing to its high selectivity and good photo stability, NIMS was successfully applied to capture super-resolution fluorescence images of lysosomes. More importantly, real-time tracking of ly so some movement in a single living cell by NIMS was realized with a confocal laser scanning microscope. Surprisingly,even in normal culture conditions, around 2/3 of the captured lysosomes were observed to move within 5 min, indicative of the highly dynamic features of lysosomes. Thus, this probe may facilitate the understanding of the ly so some dynamics in physiologicalor pathological conditions.
Superparamagnetic iron oxide(SPIO)nanoparticles are excellent magnetic resonance contrast agents and surface engineering can expand their applications.When covered with amphiphilic alkyl-polyethyleneimine(PEI),the modified SPIO nanoparticles can be used as MRI visible gene/drug delivery carriers and cell tracking probes.However,the positively charged amines of PEI can also cause cytotoxicity and restricts their further applications.In this study,we used lactose to modify amphiphilic low molecular weight polyethylenimine(C_(12-)PEI_(2K))at different lactosylation degree.It was found that the N-alkyl-PEI-lactobionic acid wrapped SPIO nanocomposites show better cell viability without compromising their labelling efficacy as well as MR imaging capability in RAW 264.7 cells,comparing to the unsubstituted ones.Besides,we found the PEI induced cell autophagy can be reduced via lactose modification,indicating the increased cell viability might rely on down-regulating autophagy.Thus,our findings provide a new approach to overcome the toxicity of PEI wrapped SPIO nanocomposites by lactose modification.
Jiuju DuWencheng ZhuLi YangChangqiang WuBingbing LinJun WuRongrong JinTaipeng ShenHua Ai
Superparamagnetic iron oxide （SPIO） nanoparticle clusters are one unique form which can enhance magnetic relaxivity and improve the magnetic resonance imaging contrast at the same iron concentration, comparing to single SPIO nanoparticles. Controlling of cluster size and other structural parameters have drawn great interests in this field to further improve their magnetic properties. In this study, we investigated how the interparticle distance （also known as neighbor distance） of SP10 nanocrystals within clusters affect their magnetic relaxation behaviors. To adjust the neighbor distance, different amount of cholesterol （CHO） was chosen as model spacers embedded into SPIO nanocluster systems with the help of amphiphilic diblock copolymer poly（ethylene glyco）-polyester. Small- angle X-ray scattering was applied to quantify the neighbor distance of SPIO clusters. The results demonstrated that the averaged SPIO nanocrystal neighbor distance of nan- oclusters increased with higher amount of added CHO. Moreover, these SPIO nanocrystal clusters had the promi- nent magnetic relaxation properties. Simultaneously, con- trolling of SPIO nanocrystal neighbor distance can regulate the saturation magnetization （Ms） and magnetic resonance （MR） T2 relaxation of the aggregation, and ultimately obtain better MR contrast effects with decreased neighbor distance.
Dan WangBingbing LinTaipeng ShenJun WuChunchao XiaBin SongHua Ai
